Anaemia I Flashcards

1
Q

Define anaemia.

A

Hb level below normal.

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2
Q

What are ‘normal’ Hb levels affected by?

A

Age

Sex

Pregnancy

Altitude

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3
Q

Effects of anaemia

A

A slightly depressed Hb level may be asymptomatic (Hb 70-100 g/L)

More severe or impaired cardiorespiratory system

  • Tiredness
  • Palpitations
  • Short of breath
  • Angina
  • Cardiac failure
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4
Q

What determines the Hb level?

A

The Hb level is a balance between:

  • Production of RBC in bone marrow, which needs:
    • Normal blood forming cells
    • Haematinics and hormones (EPO)
    • Absence of inhibitors (inflammatory cytokines)
  • Shortened time of RBC in circulation
    • Blood loss from circulation: haemorrhage
    • Shortened RBC life span: haemolysis

A change in level of Hb can either be a failure of production or increased breadown or loss.

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5
Q

Reticulocyte count

A
  • Measure of recently produced RBC (1-2 days old)
  • Measure of marrow erythropoietic activity.
    • Increased = healthy marrow response to anaemia
    • Reduced/low-normal = ?marrow (production) pathology
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6
Q

Haematinics

A

Iron studies

B12 and folate

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7
Q

Tests for haemolysis

A

Bilirubin, haptoglobin, LDH

Measure of increased RBC breakdown.

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8
Q

Bone marrow aspirate and trephine

A

Assesses marrow activity, function +/- presence of abnormal cells

Aspirate

  • Cellular details
  • Iron stores

Trephine

  • Overall view of BM structure
  • Better assessment of cellularity
  • Patchy abnormalities e.g. lymphoma
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9
Q

Classification of anaemias

A

**Decreased production **(synthetic failure) vs. **increased destruction/loss **(bleeding, haemolysis…)

or

**MCV **(mean corpuscular volume of RBC)

  • Microcytic = ‘too small’
  • Normocytic = ‘just right’
  • Macrocytic = ‘too big’
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10
Q

Microcytic anaemic causes

A
  • Iron deficiency
  • Anaemia of chronic disease (ACD)
  • Thalassaemias/haemoglobinopathies
  • Others
    • Congenital sideroblastic anaemia (rare)
    • Lead poisoning
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11
Q

Microcytic anaemia common features

A

Failure of adequate Hb incorporation into RBC.

Iron deficiency: lack of iron for haem.

ACD: block of iron transfer into RBC

Thalassaemia/haemoglobinopathies: problem with production of globin chain for Hb molecule.

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12
Q

Anaemic of chronic disease

A
  • May be microcytic of normocytic.
  • Also may be hypochromic or normochromic.

Irons stores fail to incorporate iron into RBC.

  • BM resistant to EPO
  • Inadequate production of EPO in response to anaemia

Not helped by iron therapy (can have mixed Fe deficiency and ACD).

Treat underlying cause + EPO *may *help.

Iron findings

  • Transferrin low: production inhibited in inflammation, acute phase response.
  • Serum ferritin high: increased body iron stores, increased in inflammation (acute phase)
  • BM iron increased: increased iron in macrophages.

Causes

  • infection
  • Inflammatory disorders: rheumatoid, SLE etc
  • Malignancy
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13
Q

Iron studies in iron deficiency

A

Never look at serum iron.

Ferritin reduced = iron deficiency

_Ferritin _normal/low-normal = ?iron defiency

  • Acute phase response
  • Look at transferrin saturation (if reduced - iron deficiency is likely)
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14
Q

Causes of iron deficiency

A

Blood loss

  • Iron deficiency in an adult Australian is bowel cancer until proven otherwise

Dietary

  • Vegetarians/vegans
  • Infants (cow milk protein/lactose intolerance), adolescents
  • Pregnancy (increased requirement)
  • Menorrhagia/increased requirement
  • Elderly

Malabsorption

  • Coeliac disease
  • Crohn’s
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15
Q

Causes of macrocytic anaemia

A

Magaloblastic

  • B12, folate, medication (folate depletion - e.g. MTX), BM disorders.

Non-megaloblastic

  • Increased reticulocyte count e.g. acute bleed or haemolysis
  • Normal reticulocyte count
    • Liver disease/alcohol
    • Hypothyroidism
    • Bone marrow disorders

Spurious

  • E.g. Myeloma
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16
Q

Blood film findings in megaloblasic anaemia

A
  • Single/pancytopenia
  • Macrocytosis +/- oval macrocytes
  • Hypersegmented neutrophils
17
Q

Vitamin B12 deficiency causes

A

Dietary

  • Rarely except strict vegans

Malabsorption

  • Lack of instrinsic factor
    • Pernicious anaemia
    • Gastrectomy
  • Intrinsic factor present
    • Terminal Ileal disease (IBD) or resection

Metabolic causes (rare)

18
Q

Effects of B12 deficiency

A

Dividing cells and neurological

  • Megaloblastic anaemia
  • Gastrointestinal effects
  • Neurological
    • Peripheral neuropathy
    • Subacute combined degeneration of cord
    • Other (delirium screen)
19
Q

Haemoglobinopathies

A

Thalassaemia

Haemoglobin variants

20
Q

Thalassaemia

A

Decreased rate of production of one of the globin chains, causing an ‘imbalance’ and therefore red cell changes.

Alpha thalassaemia: decreased production of alpha globin chains

Beta thalassaemia: decreased production of beta globin chains

21
Q

Haemoglobin variants

A

Production of Hb with an abnormal globin chain e.g. HbS

Most common is sickle cell disease

Amino acid substitution in globin chain.

22
Q

Alpha thalassaemia

A

Number of alpha genes deleted

  • One or two: alpha thal trait (asymptomatic)
  • Three: Hb H disease (mild to moderate disease)
  • Four: hydrops fetalis (incompatible with life)
23
Q

Homozygous alpha thalassaemia

A

Hydrops fetalis

4 alpha globin genes deleted.

Cannot make HbF, HbA or HbA2

Severe anaemia

Fatal pre-term

24
Q

Beta thalassaemias

A

Decreased production of beta globin chain

Homozygous: severe disease

Heterozygous: asympotmatic, microcytic RBC

25
Q

Homozygous beta thalassaemia

A

Marked decrease in HbA (decreased beta globin chains, excess alpha globin chains).

Symptoms from age 3-6 months (HbF)

Severe anaemia plus:

  • Erythroid hyperplasia ++ and bony malformations
  • Hepatosplenomegaly
  • Iron overload
    • Cardiomyopathy, endocrine disorders etc.

Transfusion dependent for life

26
Q

Haemoglobin E

A

Substitution one amino acid in beta globin chain.

Common in South East Asia.

HbE homozygous and heterozygous

  • Asymptomatic
  • Low MCV and blood film changes only

Double heterozygote HbE + beta thal

  • Severe disease (like beta thal major)
27
Q

Haemoglobin S

A

Substitution one amino acid in beta globin chain.

HbS less soluble and precipitates in hypoxia (sickling)

_Heterozygous HbS (_sickle cell trait)

  • Asymptomatic with normal FBC and film

Homozygous HbS (sickle cell anaemia)

  • Severe disease
  • Anaemia, sickle cell crises with pain and vascular occlusion by sickling cells
28
Q

Bone marrow failure syndromes

A

Aplasia: decrease in haemopoietic cells

Dysplasia: BM cells abnormal

Bone marrow infiltration: BM replacement

29
Q

Anaemia due to aplasia

A

General BM failure

  • Aplastic anaemia
  • Pancytopenia - low Hb, WBC and platelets

Specific to RBC

  • Pure red cell aplasia - parvovirus, autoimmune
30
Q

Bone marrow dysplasia

A

Bone marro wnromal or increased cellularity but cells look abnormal and are dysfunction.

Primary myelodysplastic syndromes

  • Acquired bone marrow genetic change
  • Often high MCV and low WBC and/or platelets

Secondary

  • Medication, pyridoxine deficiency, heavy metal poisoning
31
Q

Erythropoiesis in a dysplastic BM

A

Disturbed erythropoiesis

  • Increased RBC precursors
  • Abnormal morphology
  • Decreased RBC production (ineffective)
32
Q

Haemolytic anaemia

A

Anaemia due to shortened RBC life span.

Two sites of haemolysis

  • Extravascular (in reticuloendothelial cells)
  • Intravascular
33
Q

Evidence of haemolysis

A
  1. Morphological evidence of red cell damage
    • Spherocytes
    • RBC fragmentation
  2. Biochemical evidence of red cell breakdown
    • Increased *unconjugated bilirubin *(jaundiced)
    • Decreased haptoglobin (rapid test)
    • Increased LDH (non-specific)
  3. Increased rate of RBC production
    • Increased polychromasia (bluish RBC)
    • Increased reticulocyte count
34
Q

Causes of haemolytic anaemia

A
  1. Congenital
  2. Acquired

also classified as

  • Extrinsic (change in blood or blood vessels)
    • Autoimmune haemolytic anaemia
    • Drugs
    • DIC, mechanical valve
  • RBC membrane
    • _​_Hereditary spherocytosis
  • RBC cytoplasm
    • ​G6PD deficiency
35
Q

Investigation of haemolysis

A
  1. Is this patient haemolysing?
    • ​​FBC and blood film
    • Reticulcyte count
    • Bilirubin, urobilinogen
    • Haptoglobin
    • LDH
  2. What is the cause? Is it immune mediated (AIHA)?
    • ​​Clinical
    • RBC morphology from film
      • Spherocytes
      • Fragments
      • Specific features e.g. sickle cell
    • DAT (direct antiglobin test)
    • Other special tests
36
Q

Direct antiglobin test

A

Detects antibody on RBC

Add anti-human Ig to RBC

If antibody on RBC then added anti human Ig cross links RBC causing agglutination (DAT positive)

37
Q

Autoimmune hamolytic anaemia

A

Autoantibodies to own RBC

Increased haemolysis with spherocytes and polychromasia

DAT positive.